5-HT₃receptors participate in CCK-induced suppression of food intake by delaying gastric emptying

Abstract

Hayes, Matthew R., Rachael L. Moore, Samit M. Shah, and Mihai Covasa. 5-HT 3 receptors participate in CCK-induced suppression of food intake by delaying gastric emptying. Am J Physiol Regul Integr Comp Physiol 287: R817-R823, 2004. First published June 10, 2004 10.1152/ajpregu.00295.2004.-Serotonin type 3 (5-HT 3) receptors have been shown to participate in the negative-feedback control of food intake. We previously reported that cholecystokinin (CCK)-induced suppression of food intake is partly mediated through 5-HT 3 receptors when rats were tested on a preferred liquid diet, but whether such an effect occurs when they are tested on a solid maintenance diet is unknown. In the present study, we examined the effects of ondansetron, a selective 5-HT 3 antagonist, on CCK-induced suppression of solid chow intake. Intraperitoneal administration of ondansetron significantly attenuated 30-and 60-min CCK-induced reduction of food intake, with suppression being completely reversed by 120 min. It is not known whether 5-HT 3 receptors directly mediate CCK-induced satiation or whether their participation depends on CCK acting as part of a feedback cascade to inhibit ongoing intake. Because CCKinduced inhibition of sham feeding does not depend on additive gastric/postgastric-feedback signals, we examined the ability of ondansetron to reverse CCK-induced satiation in sham-feeding rats.Ondansetron did not attenuate reduction of sham feeding by CCK, suggesting that ondansetron does not directly antagonize CCK-satiation signals. CCK suppresses real feeding through a delay in gastric emptying. Ondansetron could attenuate CCK-induced reduction of food intake by reversing CCK-induced inhibition of gastric emptying. We found that blockade of 5-HT3 receptors attenuates CCK-induced inhibition of gastric emptying of a solid meal, as well as saline and glucose loads. We conclude that 5-HT 3 receptors mediate CCKinduced satiation through indirect mechanisms as part of a feedback cascade involving inhibition of gastric emptying. ondansetron; serotonin; osmotic; glucose; satiety GASTRIC EMPTYING IS ONE MECHANISM involved in the regulation of food intake (33, 43). A delay in gastric emptying limits the rate of absorption by reducing the rate of nutrient delivery to the small intestine (5, 15, 58) and is associated with suppression of food intake (43). Inhibition of gastric emptying is mediated by peripheral vagal and sympathetic nerves and by the release of a variety of peptides and neurotransmitters (43,54). Cholecystokinin (CCK) and serotonin [5-hydroxytryptamine (5-HT)] are two humoral signals thought to exert control on gastric emptying and are released in response to nutrients entering the duodenum (6,28,30,43,49,60). Both of these satiety signals bind to receptors on terminals of vagal afferent fibers, resulting in a delay in gastric emptying (4, 24, 49).Considerable evidence indicates that the serotonergic system participates in the negative-feedback control of food intake (for review see Ref. 25). Systemic serotonergic activity h...

Serotonin controlling feeding and satiety

“…In these experiments, CCK and 5-HT synergistically reduced food intake in a supra-additive manner, suggesting that CCK and 5-HT together bring about a stronger satiety signal than each system alone [245]. Data from the same group shows that the effects of the 5-HT3 antagonist depends on gastric signals, as gastric distension is required and the CCK antagonist, in contrast to CCK itself, is ineffective in sham-fed rats [206]. The involvement of hindbrain 5-HT3 receptors in CCK-induced satiation has been demonstrated [107].…”

“…Inducing satiety by intraduodenal fat infusion could only fully be blocked when the CCK-1 antagonist devazepide and the 5-HT3 antagonist tropisetron were administered together [242]. Such interactions between CCK and 5-HT3 antagonists have later been shown for intake of sucrose solution and also of a solid diet [206,243,244]. In these experiments, CCK and 5-HT synergistically reduced food intake in a supra-additive manner, suggesting that CCK and 5-HT together bring about a stronger satiety signal than each system alone [245].…”

“…This effect is largely relayed by the vagus to the NTS and mediated 16 by 5-HT3 receptors which are expressed on peripheral dendritic terminals of vagal afferents innervating the stomach [107,[204][205][206][207]. High densities of 5-HT3 receptor binding sites within the central nervous system have also been found in the NTS [208,209] and local administration of the 5-HT3 antagonist odansetron increased sucrose intake [107].…”

The nucleus tractus solitarius: a portal for visceral afferent signal processing, energy status assessment and integration of their combined effects on food intake

“…39,40 Gastric emptying was measured using dyedilution spectrophotometry. 41 Inhibition for food intake and gastric emptying in response to peripheral Ex-4 was comparable to intact control and decerebrate rats, as were the dose-response relationships, indicating the caudal brainstem is sufficient for mediating response production. 33 Hypothalamic processing had been hypothesized to mediate the profile of responses evoked by peripheral GLP-1R ligand delivery.…”

An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats

“…It was hypothesized that the actions of CCK may have been partly dependent on 5-HT 3 receptor activation; i.e., CCK may release 5-HT, which acts on 5-HT 3 receptors to inhibit RVLM neuronal activity. In examining the effects of CCK on feeding, many have suggested that the actions of CCK are partially dependent on 5-HT 3 receptor activation (1,6,14). Furthermore, primary vagal afferent neurons are potently stimulated by endogenous 5-HT and CCK release (26,53), and a subpopulation of nodose ganglion neurons possess high-affinity CCK 1 receptors and 5-HT 3 receptors (24).…”